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Significance Our work identified membrane cholesterol as a new inhibitor of human voltage-gated proton channel hHv1. Using single-molecule fluorescence resonance energy transfer (smFRET), we further showed that cholesterol inhibits the… Click to show full abstract
Significance Our work identified membrane cholesterol as a new inhibitor of human voltage-gated proton channel hHv1. Using single-molecule fluorescence resonance energy transfer (smFRET), we further showed that cholesterol inhibits the hHv1 channel by stabilizing the voltage-sensing S4 segment at resting conformations, a similar mechanism also utilized by Zn2+ inhibition. Our findings provided a new mechanism that the hHv1 channel regulates human fertilization by linking the cholesterol efflux with intracellular alkalization, thus sperm hyperactivation.
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Year Published: 2022
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